Pump and injector for liquid chromatography

ABSTRACT

A combined pump-injector valve system utilizing a monolithic body to provide the barrel of the pump and as the stator of the valve, thus eliminating any need for connections between a pump and a valve, and therefore the potential for high-pressure leaks or pressure reductions. The combined pump-injector valve permits injection of nanoliter-sized samples into a chromatographic column, which is sealed during loading of the sample and filling of the pump, such that complete analyses can be completed with microliters of mobile phase with nanoliters of a sample. The pump-injector valve system further includes a pressure sensor external the barrel of the pump and may include an interim position intermediate loading and injection where the contents of the barrel may be pressurized to a desired pressure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part and claims the benefit ofU.S. Non-Provisional patent application Ser. No. 14/333,661 entitled“Pump and injector for liquid chromatography” filed Jul. 14, 2014 and ofU.S. Non-Provisional patent application Ser. No. 14/156,197 entitled“Pump and injector for liquid chromatography” filed on Jan. 15, 2014,which claim the benefit of U.S. Provisional Patent Application No.61/753,299 entitled “Integral nano-scale pump and injector for highperformance liquid chromatography” filed on Jan. 16, 2013 in the UnitedStates Patent and Trademark Office, and which are incorporated herein byreference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable.

BACKGROUND OF THE INVENTION

1. Field of Invention

The present invention pertains to pump and injection valve systems foruse with liquid chromatography. More particularly, the present inventionpertains to a combined pump/injection valve for injection of ananoliter-sized sample into a chromatography column utilizing an singlepiece as the barrel of the pump and as the stator of the valve, thuseliminating any need for connections between the pump and valve.

2. Description of the Related Art

High performance liquid chromatography (HPLC) is generally performedusing pumps, columns and injection valves scaled to deliver fluids atflow rates measured in cubic centimeters of fluid per minute. Thesecomponents are typically separate and joined together to provide asystem for HPLC. Unfortunately, these systems require relatively largesample volumes, large mobile phases, and large flow rates for analysis.

Additionally, these relatively large systems frustrate generate of fieldportable HPLC units, where there is a need for a lightweight robust flowsystem which uses a minimum of mobile phase during an analysis.

It would therefore be desirable to provide an integrated nano-scale pumpand injection valve for high performance liquid chromatography.

SUMMARY OF THE INVENTION

The present invention therefore meets the above needs and overcomes oneor more deficiencies in the prior art by providing a combinedpump/injector valve which injects nanoliter samples into achromatographic column, which is sealed during loading of the sample andfilling of the pump, such that complete analyses can be completed withmicroliters of mobile phase, ranging from as small as about 5-10nanoliters, to 60 nanoliters, and larger. The present inventiontherefore provides a lightweight robust flow system which uses a minimumof mobile phase during an analysis and is appropriate for use as a fieldportable HPLC unit.

The present invention provides an integral nano-scale pump and injectionvalve for high performance liquid chromatography which includes anintegrated barrel-stator, which has an elongate barrel in a first endand a stator at a second end, a plunger slidably disposed within aninterior chamber of the barrell of substantially uniform cross-section,and a rotor, wherein the pump and injection valve is switchable betweena load position and a injection position. In one embodiment, thecircular rotor has a surface adjacent the stator and has a plurality ofchannels in its surface and is with respect to the stator about acenterpoint between the load position and the injection position. Theelongate barrel portion of the integrated barrel-stator includes an openends, a length, and a sidewall defining the interior chamber adapted toreceive a supply of fluid, an outer diameter, and a wall thickness. Thecircular stator has an orifice therethrough at its centerpoint and afirst side and a second side such that the elongate barrel open distalend is aligned with the second side of the stator at the centerpoint andthe interior chamber includes the orifice. The pump is therefore incommunication with the valve at the orifice.

In a first embodiment, the rotor includes three channels and the statorhas a first stator port for communication with a mobile phase supply, asecond stator port in communication with a fifth stator port, a thirdstator port for communication with a sample reservoir, a fourth statorport for sample outflow, a sixth stator port for communication with achromatography column, a seventh stator port for return from thechromatography column, and an eighth stator port for outflow from thevalve. In the first embodiment, the load position is defined by thefirst port and the orifice communicating with a first channel and by thethird port and the fourth port communicating with a second channel. Inthe first embodiment, the injection position is defined by the orificeand the second port communicating with the first channel, by the fifthport and the sixth port communicating with the second channel, and bythe seventh port and the eighth port communicating with the thirdchannel.

In the alternative embodiment, the rotor includes four channels and thestator has a first stator port for communication with a mobile phasesupply, a second stator port in communication with a fifth stator portvia an external loop, a third stator port for communication with asample reservoir, a fourth stator port for sample outflow, a sixthstator port for communication with a chromatography column, a seventhstator port for return from the chromatography column, and an eighthstator port for outflow from the valve. In the alternative embodiment,the load position is defined by the first port and the orificecommunicating with a first channel, by the second port and the thirdport communicating with the second channel, and the fourth port and thefifth port communicating with the third channel. In the alternativeembodiment, the injection position is defined by the orifice and thesecond port communicating with the first channel, by the fifth port andthe sixth port communicating with the third channel, and by the seventhport and the eighth port communicating with the fourth channel.

In a further alternative embodiment, where the embodiment is used as apump without regard to the equipment connected thereto, the rotor hasonly one channel and the stator has a first stator port forcommunication with a mobile phase supply and a second stator port forcommunication with an external device. In the further alternativeembodiment, the load position is defined by the first port and theorifice communicating with a first channel and the injection position isdefined by the orifice and the second port communicating with the firstchannel.

In an additional alternative embodiment, wherein the embodiment is usedto push sample through a column, but wherein the output of the column isprovided to other equipment rather than through the valve, theembodiment includes channels and the stator has a first stator port forcommunication with a mobile phase supply, a second stator port incommunication with a fifth stator port via an external loop, a thirdstator port for communication with a sample reservoir, a fourth statorport for sample outflow, and a sixth stator port for communication witha chromatography column. In the additional alternative embodiment, theload position is defined by the first port and the orifice communicatingwith a first channel, by the second port and the third portcommunicating with the second channel, and the fourth port and the fifthport communicating with the third channel. In the alternativeembodiment, the injection position is defined by the orifice and thesecond port communicating with the first channel, and by the fifth portand the sixth port communicating with the third channel.

In each embodiment, it may be advantageous to determine the pressurewithin the barrel and even to provide an interim position between theload position and the injection position, which may be characterized asa dead or pressuring position, which has no connectivity and thuspermits the fluid received in the load position to be pressurized to adesired pressure.

Additional aspects, advantages, and embodiments of the invention willbecome apparent to those skilled in the art from the followingdescription of the various embodiments and related drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

So that the manner in which the described features, advantages, andobjects of the invention, as well as others which will become apparent;are attained and can be understood in detail; more particulardescription of the invention briefly summarized above may be had byreferring to the embodiments thereof that are illustrated in thedrawings, which drawings form a part of this specification. It is to benoted, however, that the appended drawings illustrate only typicalpreferred embodiments of the invention and are therefore not to beconsidered limiting of its scope as the invention may admit to otherequally effective embodiments.

In the drawings:

FIG. 1 is an illustration of a top view of one embodiment of the presentinvention as assembled.

FIG. 2 is an illustration of a side view of one embodiment of thepresent invention as assembled.

FIG. 3 is an illustration of the face of the stator of the integratedbarrel-stator of the first embodiment of the present invention.

FIG. 4 is an illustration of the face of the rotor of the firstembodiment of the present invention.

FIG. 5 is an illustration of the relative positions of the face of thestator and the face of the rotor of the first embodiment of the presentinvention in the load position.

FIG. 6 is an illustration of the relative positions of the face of thestator and the face of the rotor of the first embodiment of the presentinvention in the injection position.

FIG. 7 is a cross-section illustration of the present invention alongline Z-Z of FIG. 1 for the maximum position of the pump associated withthe load position in connection with a linear actuator.

FIG. 8 is a cross-section illustration of the present invention alongline Z-Z of FIG. 1 for the maximum position of the pump in the injectionposition in connection with a linear actuator.

FIG. 9 is a close-up of the pump plunger driven forward for delivery forthe maximum position of the pump in the injection position.

FIG. 10 is an illustration of isometric view of the embodiment of thepresent invention with the pump and valve actuators illustrating thefirst valve position illustrated in FIGS. 5 and 7 at the maximumposition of the pump in the load position.

FIG. 11 is an illustration of isometric view of the embodiment of thepresent invention with the pump and valve actuators illustrating thesecond valve position illustrated in FIGS. 6 and 8 at the maximumposition of the pump in the injection position.

FIG. 12A is an enlargement of Section A of FIG. 10.

FIG. 12B is an enlargement of Section B of FIG. 11.

FIG. 13 is an illustration of the face of the stator of the integratedbarrel-stator in the alternative embodiment of the present invention.

FIG. 14 is an illustration of the face of the rotor of the alternativeembodiment of the present invention.

FIG. 15 is an illustration of the relative positions of the face of thestator and the face of the rotor of the alternative embodiment of thepresent invention in the load position.

FIG. 16 is an illustration of the relative positions of the face of therotor and the face of the rotor of the alternative embodiment of thepresent invention in the injection position.

FIG. 17 is an illustration of the relative positions of the face of thestator and the face of the rotor of the further alternative embodimentof the present invention in the load position.

FIG. 18 is an illustration of the relative positions of the face of therotor and the face of the rotor of the further alternative embodiment ofthe present invention in the injection position.

FIG. 19 is an illustration of the relative positions of the face of thestator and the face of the rotor of the additional alternativeembodiment of the present invention in the load position.

FIG. 20 is an illustration of the relative positions of the face of therotor and the face of the rotor of the additional alternative embodimentof the present invention in the injection position.

FIG. 21 is a close-up of the pump plunger driven forward for deliveryfor the maximum position of the pump in the injection position depictinga seal of the present disclosure.

FIG. 22 is an illustration of the relative positions of the face of thestator and the face of the rotor of the additional alternativeembodiment of the present invention in the load position.

FIG. 23 is an illustration of the relative positions of the face of thestator and the face of the rotor of the additional alternativeembodiment of the present invention in the injection position.

FIG. 24 is an illustration of a strain gauge, as a pressure sensor,incorporated about the integrated barrel-stator.

FIG. 25 is an illustration of the face of the rotor of the presentinvention identifying the location of the interim position.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring to FIGS. 1 and 2, a two-position embodiment of the integratednano-scale pump and injection valve 100 is provided. A top view of oneembodiment of the integrated nano-scale pump and injection valve 100 asassembled is provided in FIG. 1 while a side view is provided FIG. 2. Asillustrated in FIGS. 1B and 2, the integrated nano-scale pump andinjection valve 100 includes an integrated barrel-stator 716 whichprovides the interface between the pump section 102 and valve section104.

Referring to FIGS. 3 and 4, constructions of the face of the stator 302and the face of the rotor 402 of the integrated barrel-stator 716 areillustrated for a first embodiment. Referring to FIGS. 13 and 14,constructions of the face of the stator 302 of the integratedbarrel-stator 716 and the face of the rotor 1402 of the valve section104 are illustrated for an alternative embodiment.

Referring to FIGS. 1-22, by forming the elongate barrel 726 of the pump708 and the stator 302, 1302, 1712, 1932 of the valve 710 of a singlepart as integrated barrel-stator 716, the integrated nano-scale pump andinjection valve 100 may operate at high pressures without degradationincident to intervening parts and fittings.

Unlike the prior art where a valve and pump were separate bodies simplyjoined together, in the integrated nano-scale pump and injection valve100, as illustrated in FIGS. 7-12B, the elongate barrel 726 of the pump708 and the stator 302, 1302, 1712, 1932 of the valve 710 are integrallyformed of a single piece, i.e a monolithic body, to provide directcommunication between the pump 708 and the valve 710 without introducingany fittings or connectors which may swell or leak during high pressureoperation.

By switching between the maximum extent of the load position 502, 1502,1710, 1928 and the maximum extent of the injection position 602, 1602,1802, 2002, the integrated nano-scale pump and injection valve 100provides a pump 708, which may be sized to hold microliters for use withnano-scale columns for quick separation.

Upon initiation of loading, the pump 708 and valve 710 and positioned inthe load position 502 and the plunger 706 begins being retracting by thepiston 712 and draws a solvent from a reservoir, such as through a 15cm×200 μm steel tube into the barrel 726. At the same time andindependent of pump filling, a sample is introduced into the sample loopthrough a 5.08 cm×75 μm inner diameter capillary, which is connected tothe port 308 on the pump and to a sample supply, preferably using azero-dead volume connector.

After completion of loading, the integrated nano-scale pump andinjection valve 100 may be switched for injection, changing thedirection of operation of the pump 708 and changing the position of thevalve 710. During injection, the plunger 706 is driven by the piston 712into the barrel 726. The rate of advance, and therefore the dispensingflow rate, may be controlled by power supply and/or by computersoftware. As the plunger 706 is driven forward by the piston 712, thesample is driven from the sample passage of second channel 406 into thecolumn 504 while the mobile phase flows from the barrel 726 through theloop 506, through the column 504 and to the detector.

In all embodiments, in the load position 502, 1502, 1710, 1928, the pumpplunger 706 is retracted for filling the interior chamber 702 asillustrated in FIGS. 7, 10 and 12A. The plunger may have a diameter of0.03 inches, or slightly smaller, or of 0.93 inches, or slightly larger,or may be between, such as 0.62 inches. The pump 708 thus includes apump plunger 706, an interior chamber 702 defined by an elongate barrel726 and the plunger 706. Referring to FIGS. 5, 7, 10, 12A and 15, thearrangement and nano-scale operation of integrated nano-scale pump andinjection valve 100 is illustrated in at the maximum position of thepump 708 in the load position 502. The load position 502 of integratednano-scale pump and injection valve 100, showing the positions of thestator 302 and the rotor 402 in the first embodiment, is depicted inFIG. 5. The load position 1502 of integrated nano-scale pump andinjection valve 100, showing the positions of the stator 1302 and therotor 1402 for the alternative embodiment is depicted in FIG. 15. As canbe appreciated either the stator 302, 1302, 1712, 1932 or the rotor 402,1402, 1702, 1902 will include a seal surface to contact the other. Across-section illustration of the present invention along line Z-Z ofFIG. 1 for the maximum position of the pump 708 in the load position502, 1502, 1710, 1928 is illustrated in FIG. 7. An illustration ofisometric view of the embodiment of the present invention with the valveactuator illustrating the first valve position is illustrated in FIG.10. An enlargement of Section A of FIG. 10 is provided in FIG. 12A.

Referring to FIG. 21, for operation at high pressure, such as above10000 psi, it is essential that a strong seal 2150 be positioned aboutthe plunger 706 within the barrel 726 of the integrated barrel-stator716, at least a stroke-length 1202 above or beyond the first end 750 ofthe plunger 706 when in the maximum injection position so as to contactthe plunger 706 and to form a seal thereabout. Positioning the seal 2150less than a stroke-length 1202 from the first end 750 of the plunger 706would cause the seal 2150 to fail when the plunger 706 was fullyretracted to reach the maximum load position. While a single seal acrossthe barrel 726, through which the plunger 706 would move, may be used, acomposite seal is preferable. As depicted in FIG. 21, the seal 2150about the plunger 706 within the barrel 726 may be formed of acompressed sequence of a first hard seal 2100, a flexible seal 2108, anda second hard seal 2112, placed under compression by a driving disk 2106maintained within the integrated barrel-stator 716. The diameter of thebarrel 726 of the integrated barrel-stator 716 is enlarged for thatsection more than a stroke-length 1202 above or beyond the first end 750of the plunger 706 when in the maximum injection position to accept afirst hard plastic seal 2100. The first hard plastic seal 2100 may becomposed of a material such as polyether ether ketone (PEEK) or anothermaterial, and is sized to fit within the barrel 726 and about theplunger 706 without precluding movement of the plunger 706. Atop thefirst hard plastic seal 2100 is positioned a flexible seal 2108. Theflexible seal 2108 is composed of a compressible sealing material, suchas polytetrafluoroethylene (PTFE). The flexible seal 2108 is sized tofit within the barrel 726 and about the plunger 706 without precludingmovement of the plunger 706. Atop the flexible seal 2108 is positioned asecond hard plastic seal 2112, which may also may be composed of amaterial such as polyether ether ketone (PEEK) or another material, andis sized to fit within the barrel 726 and about the plunger 706 withoutprecluding movement of the plunger 706. Compression of the flexible seal2108 results in lateral expansion of the flexible seal 2108 and therebycauses the flexible seal 2108 to provide a seal against the plunger 706which does not preclude movement of the plunger 706, between the firsthard seal 2100 and the second hard seal 2112. This may be accomplishedby application of force against the second hard seal 2112 and a shoulder2114 in the barrel 726 to maintain the position of the first hard seal2100. The application of force against the second hard seal 2112 may beobtained by joining a threaded male sleeve or nut 2102, having a boretherethrough to freely accommodate the plunger 706 and piston 712without interference, to the integrated barrel-stator 716, above orbeyond the seal 2150, which threaded male sleeve 2102 would apply forceto one or more springs 2122, particularly a Belleville spring also knownas a coned disc spring, positioned within the integrated barrel-stator716 above or adjacent the barrel 726, to force a driving disk 2106 tocompress the second hard seal 2112. The threaded male sleeve 2102 issized to a threaded female section of the integrated barrel-stator 716above or adjacent the barrel 726. The driving disk 2106 includes a bore2124 sized to permit the plunger 706 to pass therethrough withoutinterference, a shoulder 2116 to permit the application of force againstthe driving disk 2106 from the springs 2122 smaller in diameter than thethreaded male sleeve or nut 2102 so as not to contact the inner walls ofthe integrated barrel-stator 716, and a neck 2120 at its end 2126proximate the barrel 726 sized to enter the barrel 726 withoutinterference and having sufficient height to contact and apply forceagainst the second hard seal 2112. As a result, the neck 2120 is drivenagainst the second hard seal 2112, which is in turn driven into theflexible seal 2108 to compress it and form a seal about the plunger 706.The plunger 706 is therefore able to move through the seal 2150 withoutfluid seeping past, even as the flexible seal 2108 may become pliableduring repeated movement of the plunger 706. Because only the seals2112, 2108, 2100 laterally contact the plunger 706, and because thebalance of the components, including the integrated barrel-stator 716,the threaded male nut or sleeve 2102, and the driving disk 2106, includesufficient clearance for the plunger 706 to move without interference,the plunger 706 can move within the barrel 726 and can operate to drawor eject fluid into the barrel 726 and through the stator 302,particularly at high pressure.

Thus, the seal 2150 includes a first hard plastic seal 2100, a flexibleseal 2108, a second hard plastic seal 2112 and is compressed to sealabout the plunger 706 by a driving disk 2106, a threaded male sleeve2102, and one or more springs 2122. The first hard plastic seal 2100 issized to fit within the barrel 726 and to fit about the plunger 706. Theflexible seal 2108 is sized to fit within the barrel 726 and to fitabout the plunger 706 adjacent the first hard plastic seal 2100. Thesecond hard plastic seal 2112 is sized to fit within the barrel 726 andto fit about the plunger 706 adjacent the flexible seal 2108. Thedriving disk 2106 has a bore 2124 therethrough sized to fit about theplunger 706 without interference, a first end 2118 and a second end2126. The driving disk 2106 is sized to freely fit within saidintegrated barrel-stator 716 adjacent the barrel 726, and includes ashoulder 2116 near the first end 2118, and a neck 2120 at the second end2126, which neck 2120 is sized to fit within the barrel 726 and tocontact the first hard plastic seal 2100. The threaded male sleeve 2102has a bore therethrough sized to permit movement of the plunger 706without interference and is sized to a threaded female section withinthe integrated barrel-stator 716 above, or adjacent, the barrel 726. Thespring 2122 contacts the shoulder 2116 of the driving disk 2106 and anend of said threaded male sleeve 2102 and is compressed as the threadedmale sleeve 2102 is driven into the integrated barrel-stator 716.

Referring to FIG. 5, in the first embodiment, the valve 710 thus has acircular stator 302, formed integrally with the elongate barrel 726 of asingle block of monolithic material, to provide the integratedbarrel-stator 716, and a circular rotor 402 where the two componentscooperate to permit or preclude fluid communication among various partsof the valve 710. The stator 302 has an orifice 320 at its centerpoint,as well as a first stator port 304 for communication with a mobile phasesupply, a second stator port 306 in communication with a fifth statorport 312, a third stator port 308 for communication with a samplereservoir, a fourth stator port 310 for outflow of sample waste, a sixthstator port 314 for communication with a chromatography column 504, aseventh stator port 316 for return from the chromatography column 504,and an eighth stator port 318 for outflow from the valve 710 such as toa detector. As both ends of the column 504 can be connected to theintegrated nano-scale pump and injection valve 100 to maintain pressureduring filling of the integrated nano-scale pump and injection valve 100when the flow through the column 504 is stopped, if desired. This wouldeliminate a delay period for column re-pressurization. The rotor 402therefore has a surface adjacent the stator 302 and three channels, orslots, 404, 406, 408 in its surface. The rotor 402 is rotatable withrespect to the stator 302 about the centerpoint between the loadposition 502 and the injection position 602. Rotation between the twopositions may be 45 degrees about the centerpoint, or more or less. Inthe load position 502, components are isolated while the mobile phase isdelivered to the internal chamber 702 of the pump 708, so that the firstport 304 communicates with the orifice 320, and thereby to the internalchamber 702 of the pump 708, via the first channel 404, to providefilling, while all other ports are individually or paired in isolation,include the third port 308 and the fourth port 310, while communicatingvia the second channel 406 not otherwise communicating with any othercomponents. The column 504 may therefore maintained at pressure andisolated while the interior chamber 702 of the pump 708 located in thepump section 102, as illustrated in FIG. 7, is filled by a mobile phaseby drawing mobile phase through orifice 320, introduced via firstchannel 404 which is connected to port 304. For initial charging of thecolumn 504, the operator can run the mobile phase through the secondchannel 406, the sample channel, switching between the load position 502and the injection position 602 to fill the column 504 and to ensure nobubbles are present in the system. In the load position 502, the port318, which may be connected to a detector, is likewise isolated.Referring to FIGS. 3 and 4, and more particularly to FIG. 5, in thisload position 502, with reference to stator 302 and rotor 402, ports 306and 312 are in communication to form a loop 506, to provide an internalsample, but are otherwise isolated. This loop 506 may be of 5.08 cm×75or 150 μm inner diameter stainless steel tubing to carry the mobilephase to the column during injection (dispensing). A sample isintroduced to and flows through the integrated nano-scale pump andinjection valve 100 at port 308, the sample inlet port, which isconnected via second channel 406 to port 310, the waste outlet port. Ascan be appreciated each port is associated with a connector 206 on theintersection of the pump section 102 and the valve section 104. Duringthe introduction of the sample, second channel 406 therefore containsthe sample to be tested. Thus, in this load position 502, a sample,which may originate from an external reservoir, may be flowed through aninternal passage. In the injection position 602, mobile phase isdelivered from the pump 708 and directed through the valve 710 to thecolumn 504 and potentially to a downstream detector by connecting theorifice 320, which is in communication with the pump 708, and the secondport 306 via the first channel 404, by connecting the fifth port 312 andthe sixth port 314 via the second channel 406, which thereby provides acomplete flow path to the chromatography column 504, and by connectingthe seventh port 316, which is in communication with the outflow of thecolumn 504, with the eighth port 318 via the third channel 408 so thatthe sample separated by the column 504 may be processed by a detector.As can be appreciated, in a secondary embodiment, the seventh port 316,the eighth port 318 and the third channel 408 could be omitted and theoutflow from the column 504 provided directly to a detector or otherequipment.

Due to the volumes involved, refilling of the integrated nano-scale pumpand injection valve 100 may be accomplished is less than 2 minutes.Since typical flow rates used in capillary columns (100-150 μm i.d.)range from 100 to 500 nL/min, an isocratic separation can be easilycompleted without the need to refill the integrated nano-scale pump andinjection valve 100.

In the alternative embodiment, such as depicted in FIGS. 13, 14, 15, and16, the valve 710 has a circular stator 302, again of a single block ofmonolithic material to also provide the elongate barrel 726, formedintegrally therewith, and a circular rotor 402 where the two componentscooperate to permit or preclude fluid communication among various partsof the valve. As with the stator of the first embodiment, the stator1302 has an orifice 1320 at its centerpoint with the pump 708 incommunication with the valve 710 at the orifice 1320, a first statorport 1304 for communication with a mobile phase supply, a second statorport 1306 in communication with a fifth stator port 1312 via a loop1506, a third stator port 1308 for communication with a samplereservoir, a fourth stator port 1310 for outflow, a sixth stator port1314 for communication with a chromatography column 1504, a seventhstator port 1316 for return from the chromatography column 1504, and aneighth stator port 1318 for outflow from the valve 710 such as to adetector. The rotor in the alternative embodiment includes the fourchannels 1404, 1406, 1408, 1410 in its surface. In the alternativeembodiment, the load position 1502 is defined by the first port 1304 andthe orifice 1320 communicating with the first channel 1404, by thesecond port 1306 and the third port 1308 communicating with the secondchannel 1406, and the fourth port 1310 and the fifth port 1312communicating with the third channel 1408. In the alternativeembodiment, as illustrated in FIG. 15, the column 504 is attached toport 1314, column inflow, and port 1316, column outflow, which areotherwise isolated. The column 1504 is therefore maintained at pressureand isolated while the interior chamber 702 of the pump 708 located inthe pump section 102, as illustrated in FIG. 7, is filled by a mobilephase by drawing mobile phase through orifice 1320, introduced via thefirst channel 1404, the fill/dispense channel, which is connected toport 1304. In the load position 502, the port 318, which may beconnected to a detector, is likewise isolated. Referring to FIGS. 13 and14, and more particularly to FIG. 15, in this load position 502, withreference to stator 1302 and rotor 1402, ports 1306 and 1312 are incommunication to form a loop 1506 but are otherwise isolated. A sampleis introduced to and flows through the integrated nano-scale pump andinjection valve 100 at port 1308, the sample inlet port, which isconnected via second channel 1406 to port 1306 and then, via a loop 1506to port 1312, which is then in communication with port 1310 via thirdchannel 1408, the waste outlet port. As can be appreciated each port isassociated with a connector 206. During the introduction of the sample,the sample to be tested is contained with the channel 1406 and the loop506, providing for an increased sample size. Thus, in this load position502, a sample, which may originate from an external reservoir, may beflowed through an internal passage. In the alternative embodiment, theinjection position 1602 is defined by the orifice 1320 and the secondport 1306 communicating with the first channel 1404, by the fifth port1312 and the sixth port 1314 communicating with the third channel 1408,and by the seventh port 1316 and the eighth port 1318 communicating withthe fourth channel 1410.

In the first embodiment, the second channel 406 defines the nano-scalesample size while the interior chamber 702 contains the volume fromwhich mobile phase is pumped. In the alternative embodiment, the thirdchannel 1408 and the loop 1506 define the nano-scale sample size.

Referring to FIGS. 6, 8, 9, 11, and 12B, the nano-scale operation of thepump section 102 is illustrated in the injection position 602 for thefirst embodiment. The injection position 602 of the nano-scale operationof the pump section 102, showing the positions of the stator 302 and therotor 402, is depicted in FIG. 6. As illustrated in FIG. 6, the rotor isrotated 45 degrees, preferably by a mechanical valve actuator 202coupled to act in concert with the action of the linear pump actuator204, generating a new flow path within the valve 710. The relativeposition between the stator 302 and the rotor 402 may be set to providefor a greater or lesser rotation. Referring to FIG. 6, the first channel404, the fill/dispense channel, connects the internal pump 708, viaorifice 320, to the loop 506 at port 312. The loop 506 now connects tosecond channel 406 containing the sample. Ports 308 and 310 are nowisolated, preventing further inflow of any sample. Similarly, port 304is isolated, preventing further inflow of mobile phase. As secondchannel 406 containing the sample now connects to the inlet of thecolumn 504 via port 314 and as channel 408 now connects the outlet ofthe column 504, at port 316, to the port 318, the outlet to thedetector, a complete flow path is established and the mobile phasepushes the sample through the column 504 and to any connected detector.This is accomplished by the pump plunger 706 being driven toward thevalve 710 as illustrated in FIGS. 8, 10 and 12B, displacing fluid fromthe interior chamber 702 into the valve 710. Thus, the pump 708 deliversfluid through the sample passage of second channel 406 into the column504. When the drive shaft 730 of the valve 710 is rotated by a valveactuator 202, the pump 708 is started, which results in the pump 708starting the moment the endpoint is reached and thus avoids the columnbed becoming unstable. As can be appreciated, upon completion of theanalysis, the integrated nano-scale pump and injection valve 100 isreturned to the load position 502, the filling position.

Referring to FIGS. 8, 9, 11, 12B, and 16, the nano-scale operation ofthe pump section 102 is illustrated in the injection position 1602 forthe second embodiment. The injection position 1602 of the nano-scaleoperation of the pump section 102, showing the positions of the stator1302 and the rotor 1402, is depicted in FIG. 16. As illustrated in FIG.16, the rotor is rotated 45 degrees, preferably by a mechanical valveactuator 202 coupled to act in concert with the action of the linearpump actuator 204, generating a new flow path within the valve 710. Therelative position between the stator 1302 and the rotor 1402 may be setto provide for a greater or lesser rotation. Referring to FIG. 16, firstchannel 1404, the fill/dispense channel, connects the internal pump 708,via orifice 1320, to the loop 1506 at port 1312. The loop 1506,containing some sample, connected to third channel 1408 also containingsome sample, now connects to the inlet of the column 1504 via port 1314and as third channel 1408 now connects the outlet of the column 1504, atport 1316, to the port 1318, the outlet to the detector, a complete flowpath is established and the mobile phase pushes the sample through thecolumn 1504 and to any connected detector. This is accomplished by thepump plunger 706 being driven toward the valve 710 as illustrated inFIGS. 8, 10 and 12B, displacing fluid from the interior chamber 702 intothe valve 710. Thus, the pump 708 delivers fluid into the column 504.Ports 1308 and 1310 are isolated, preventing further inflow of anysample. Similarly, port 1304 is isolated, preventing further inflow ofmobile phase. When the drive shaft 730 of the valve 710 is rotated by avalve actuator 202, the pump 708 is started, which results in the pump708 starting the moment the endpoint is reached and thus avoids thecolumn bed becoming unstable. As can be appreciated, upon completion ofthe analysis, the integrated nano-scale pump and injection valve 100 isreturned to the load position 502, the filling position.

Referring to FIGS. 17 and 18, the present disclosure may alternativelybe used as a pump without regard to the equipment connected thereto. Inthe further alternative embodiment, the rotor 1702 has a channel 1704and the stator 1712 has a first stator port 1706 for communication witha mobile phase supply, an orifice 1714 in communication with theelongate barrel 726 and a second stator port 1708 for communication withan external device. In the further alternative embodiment, the loadposition 1710, as illustrated in FIG. 17, is defined by the first port1706 and the orifice 1714 communicating with the channel 1704 and theinjection position 1802 is defined by the orifice 1714 and the secondport 1708 communicating with the channel 1704. As can be appreciated,any number of additional ports may be positioned on the stator 1712 topermit the pump to draw fluid through the first port 1706 to be pumpedto any one of a plurality of ports, providing a multiple position valve.

Referring to FIGS. 19 and 20, the present disclosure may be used to pusha sample through a column, wherein the output of the column is providedto other equipment rather than through the valve. In the additionalalternative embodiment, the rotor 1902 has a first channel 1904, asecond channel 1906, and a third channel 1926, and the stator 1932 hasthe orifice 1924 in communication with the elongate barrel 726, a firststator port 1908 for communication with a mobile phase supply, a secondstator port 1910 in communication with a fifth stator port 1912 via anexternal loop 1914, a third stator port 1916 for communication with asample reservoir, a fourth stator port 1918 for sample outflow, and asixth stator port 1920 for communication with a chromatography column1922. In the additional alternative embodiment, the load position 1928is defined by the first port 1908 and the orifice 1924 communicatingwith a first channel 1904, by the second port 1910 and the third port1916 communicating with the second channel 1906, and the fourth port1918 and the fifth port 1912 communicating with the third channel 1926.In the alternative embodiment, the injection position 2002 is defined bythe orifice 1924 and the second port 1910 communicating with the firstchannel 1904, and by the fifth port 1912 and the sixth port 1920communicating with the third channel 1926, which is connected to acolumn 1922 connected to the sixth port 1920.

Referring to FIGS. 22 and 23, the present disclosure may be used to pushan internal sample through a column, wherein the output of the column isprovided to other equipment rather than through the valve, incorporatingthe structure and flow paths of the first embodiment depicted in FIGS.3-6 excerpt for the third channel 408, and the seventh port 316 and theeighth port 318, which are omitted. FIG. 22 is an illustration of therelative positions of the face of the stator and the face of the rotorof the additional alternative embodiment of the present invention in theload position. FIG. 23 is an illustration of the relative positions ofthe face of the rotor and the face of the rotor of the additionalalternative embodiment of the present invention in the injectionposition. Referring to FIG. 22, the valve 710 has a circular stator2202, formed integrally with the elongate barrel 726 of a single blockof monolithic material to form or provide an integrated barrel-stator716, and a circular rotor 2250 where the two components cooperate topermit or preclude fluid communication among various parts of the valve710. The stator 2202 has an orifice 2220 at its centerpoint, as well asa first stator port 2204 for communication with a mobile phase supply, asecond stator port 2206 in communication with a fifth stator port 2212via a loop 2260, a third stator port 2208 for communication with asample reservoir, a fourth stator port 2210 for outflow of sample waste,and a sixth stator port 2214 for communication with a chromatographycolumn 2280. The rotor 2250 therefore has a surface adjacent the stator2202 and two channels, or slots, 2254, 2256 in its surface. The rotor2250 is rotatable with respect to the stator 2202 about the centerpointbetween the load position 2222 and the injection position 2232. Theinjection position 2232 of the nano-scale operation of the pump section102, showing the positions of the stator 2202 and the rotor 2250, isdepicted in FIG. 23. The first channel 2254, the fill/dispense channel,connects the internal pump 708, via orifice 2220, to the loop 2260 atport 2212. The loop 2260 now connects to second channel 2256 containingthe sample. Ports 2208 and 2210 are now isolated, preventing furtherinflow of any sample. Similarly, port 2204 is isolated, preventingfurther inflow of mobile phase. As second channel 2256 containing thesample now connects to the inlet of the column 2280 via port 2214,providing a complete flow path so the mobile phase pushes the samplethrough the column 2280 and to any connected detector.

The stroke of the pump section 102, as illustrated in general in FIGS. 7and 8, is particularly illustrated in FIGS. 12A and 12B, wherein thestroke 1202 of the pump section 102 is illustrated between the maximumload position 502, 1502, 1710, 1928 and the maximum injection position602, 1602, 1802, 2002. The stroke 1202 may be 0.25 inches, or slightlysmaller, or 0.75 inches, or slightly larger, or may be between, such asat 0.50 inches. As can be appreciated, the stroke 1202 and the diameterof the barrel 726 determine the volume of fluid transmitted during eachload and injection cycle, which, by virtue of their values, are measuredin microliters. Operation of the invention and the associated low flowrates are made possible by use of the integration of the pump section102 and the valve section 104, unlike conventional products.

Referring to FIGS. 7, 8, 9, 10, 11, 12A and 12B, operation of theintegrated nano-scale pump and injection valve 100 is provided by thebody 724, the linear pump actuator 204, and the integrated barrel-stator716. The linear pump actuator 204 includes a plunger-driving piston 712connected to the plunger 706. A plunger 706, at least equal in length tothe stroke 1202 and nearly-equivalent to the diameter of the interiorchamber 702, is attached to the end of the plunger-driving piston 712.In the load position 502, 1502, 1710, 1928, the plunger 706 is at itsmaximum retraction within the elongate barrel 726 and defines themaximum volume which may be moved during the stroke 1202. In theinjection position 602, 1602, 1802, 2002, the plunger 706 is at itsmaximum displacement into the elongate barrel 726. The volume displacedduring the stroke 1202 between the maximum position associated with theloading 502, 1502, 1710, 1928 and the maximum position associated withthe injection 602, 1602, 1802, 2002 is equal to the volume of theplunger 706 introduced into the elongate barrel 726. The position of theplunger 706 in the barrel 726 and its extent during the stroke bedetermined with mechanical systems such as optical encoders, or othersknown in the art, and the maximum extent may be defined and operationlimited by mechanical stops or limit switches.

Thus, the integral nano-scale pump and injection valve 100 includes abody having a pump section 102 and a valve section 104 where the bodyhas a pump 708 in the pump section 102 and a valve 710 in the valvesection 104. The pump 708 functions linearly by using an elongate barrel726 and a plunger 706. As the barrel provides an internal chamber inwhich the plunger 706 moves, drawing or ejecting fluid from one endwhile the plunger 706 is moved from the opposing end, the elongatebarrel 726 is characterized by an open proximal end, an open distal end,a length, and a sidewall, which define the interior chamber 702. Asdetailed, the internal chamber 702 is adapted to receive a supply ofmobile phase, and provides operation in connection with the plunger 706by having an inner diameter sized to the plunger, an outer diametersized to fit within the pump section and a wall thickness therebetweento provide sufficient strength. The plunger 706, which has asubstantially uniform cross-section, is slidably disposed within theinterior chamber 702 and is sized to ensure effective operation duringthe load position 502, 1502, 1710, 1928 and the injection position 602,1602, 1802, 2002.

The present invention provides an integral nano-scale pump and injectionvalve 100 for high performance liquid chromatography which includes anintegrated barrel-stator 716, which has an elongate barrel 726 at afirst end and a stator 302, 1302, 1712, 1932 at a second end, a plunger706 slidably disposed within an interior chamber 702 of the barrel 726of substantially uniform cross-section, and a rotor 402, wherein thepump 708 and valve 710 are switchable between a load position 502, 1502,1710, 1928 and a injection position 602, 1602, 1802, 2002. The circularrotor 402 has a surface adjacent the stator 302 and has a plurality ofchannels 404, 406, 408, 1404, 1406, 1408, 1410 in its surface and isrotatable with respect to the stator 302, 1302 about a centerpointbetween the load position 502, 1502, 1710, 1928 and the injectionposition 602, 1602, 1802, 2002. The elongate barrel 726 portion of theintegrated barrel-stator 716 includes an open proximal end, an opendistal end, a length, and a sidewall defining the interior chamber 702adapted to receive a supply of fluid and which has an inner diameter, anouter diameter, and a wall thickness. The circular stator 302 has anorifice 320 at its centerpoint and a first side and a second side suchthat the elongate barrel open distal end is aligned with the second sideof the stator 302 at the centerpoint and the interior chamber 702includes the orifice 320. The pump 708 is therefore in communicationwith the valve 710 at the orifice 320. Because of the integrated natureof the pump 708 and valve 710, it is desirable that the pressure bemeasured within the elongate barrel 726. Unfortunately, the integratedbarrel-stator 716 is necessarily monolithic and therefore precludes thepresence of a pressure transducer within the elongate barrel 726, orintermediate the elongate barrel 726 and the associated rotor 402. Whilethe pressure could be monitored external the valve 710, such anarrangement would frustrate the operation of the integrated nano-scalepump and injection valve system 100 as it would require a furtherpressure control system. However, as illustrated in FIG. 24, thepressure within the elongate barrel 726 may be measured external theintegrated barrel-stator 716 without any orifice or contact with theinterior or the integrated barrel-stator 716. This immediate pressuredetermination would typically be accomplished by a pressure transducerintermediate the pump and valve, but the integration of those two in thepresent invention precludes a conventional intermediate component.Therefore the integration of a pressure transducer into the presentsystem is accomplished by determining the effect of pressure of thebarrel itself. The integrated barrel-stator 716 may provide an elongatebarrel 708 having a thickness 2410 along a first side 2408 of theintegrated barrel-stator 716 on the elongate barrel 726 sufficient tosustain the operating pressure of the integrated nano-scale pump 708 andinjection valve system 100 but sufficiently thin to deformproportionally to a change in the operating pressure without failing,i.e. leaking or exploding, in a pressure-reading section 2402 andsufficiently elastic to return to its original dimension prior topressurization so that subsequent readings are consistent with aninitial position. This return to original position is essential forproper functioning and measurement of internal pressure. Any combinationof material and thickness which fails to return to its originalposition, i.e. it deforms under pressure, will fail to be usable for theintegrated barrel-stator 716. The thickness 2410 is a property of thematerial selected and the strength of the material of the integratedbarrel-stator 716, i.e. the extent to which it deforms under pressure. Astrain gauge 2404 is affixed to the elongate barrel 726 at this pressurereading section 2402 to provide a signal consistent with the extent ofthe deformation of the elongate barrel 726 while under pressure, whichbe converted to a pressure reading, thus providing a pressure sensor2406. The extent of deformation is measured in respect to the originalposition, while not under pressure. The strain gauge 2404 is thusaffixed to the integrated barrel-stator 716 at the first side 2408 andadapted to detect deflection consistent with a pressure change withinthe elongated barrel 726.

It may further be advantageous to permit the pressure at which the fluidin the pump 708 is provided from the integrated nano-scale pump andinjection valve system 100 to be altered, such as increased ordecreased, to a desired pressure. Additionally, pressure control may bedesirable where two or more integrated nano-scale pump and injectionvalve systems 100 are used in conjunction to provide a flow to at-connector, where a pressure differential between the two integratednano-scale pump and injection valve systems 100, such as incident to adifference in compressibility of the associated mobile phases, mayresult in retarded or back flow from the first integrated nano-scalepump and injection valve system 100 to the second integrated nano-scalepump and injection valve system 100. Thus, the fluid within anintegrated nano-scale pump and injection valve system 100 may bepressurized between the load position 502, 1502, 1710, 1928 and theinjection position 602, 1602, 1802, 2002 by operation of the pump, whilemonitoring pressure, while the rotor 2504 is in an interim position2502, as illustrated in FIG. 25. By operation of the pump 708 while therotor 2504 is in the interim position 2502, where the fluid containedwithin the elongate barrel 726 has no means of escape, the pressurewithin the elongate barrel 726 can be increased to the desired pressureby driving the plunger 706 toward the rotor 2504, or even decreased byretracting the plunger 706 away from the rotor 402. This interimposition 2502 may be characterized the channel 2516 being associatedwith a dead or pressurizing position 2510 on the face of the stator 2508at a location intermediate the first stator port 2512 and the secondstator port. In the interim position 2502, the orifice 2506 is exposedto the surface of the rotor 2504, which may be at a detent on thesurface of the rotor 2504. Unlike other positions on the rotor 2504, theinterim position 2502 provides no outlet. As a result, the contents ofthe plunger 706 and of the channel 2516 are pressurized prior toconnection with a second stator port 2514.

The pump 708 may be engaged while the rotor 402 is in this interimposition 2502, causing the pressure in the elongate barrel 726 to alterto the desired level. Once the desired pressure has been achieved, therotor 402 is shifted to the injection position 602, 1602, 1802, 2002.When desired, the rate of advance of the plunger 706 may then becontrolled to maintain the desired pressure, as measured by the pressuresensor 2406. The rate of advance of the plunger 706 may be varied inresponse to data from the strain gauge 2404 to maintain the desiredpressure.

The nano-scale operation of the integrated nano-scale pump and injectionvalve 100 is made possible by integration of parts may be furtheraugmented by sufficient and operable 360 zero-dead volumemicrometerfittings, and by material selection. Diamond-coated surfaces may beutilized where beneficial. The plunger 706 may be constructed of a workhardened super alloy, such as MP35N, a nickel-chromium-molybdenum-cobaltalloy providing ultra-high strength, toughness, ductility and highcorrosion resistance—particularly from contact with hydrogen sulfide,chlorine solutions and mineral acids (nitric, hydrochloric, andsulfuric). Moveover, the nano-scale operation of the integratednano-scale pump and injection valve 100 permits portability, such asbeing battery-operated, while being light weight, having low mobilephase consumption and generating low waste. Additionally, this system,designed particularly for capillary column use, does not employ asplitter, provides a substantial in operation. The integrated nano-scalepump and injection valve 100 can generate up to 110.32 MPa (16,000 psi)pressure, with a pump volume capacity of 24 μL, and a sample volume aslow as 10 nL, or higher, such as 60 nL, can be injected As a result ofthe structures provided herein, the maximum and minimum dispensingvolumetric flow rates of the integrated nano-scale pump and injectionvalve 100 are 74.2 μL/min and 60 nL/min, respectively. This may furtherbe accomplished by providing the loop 506 of 5.08 cm×75 or 150 μm innerdiameter stainless steel tubing to carry the mobile phase to the columnduring injection (dispensing).

The terms and expressions which have been employed in the foregoingspecification are used therein as terms of description and not oflimitation, and there is no intention, in the use of such terms andexpressions, of excluding equivalents of the features shown anddescribed or portions thereof.

We claim:
 1. An integral nano-scale pump and injection valve for highperformance liquid chromatography comprising: an integratedbarrel-stator, said integrated barrel-stator having an elongate barreland a stator, said integrated barrel-stator integrally-formed of asingle piece of monolithic material, said elongate barrel having a firstopen end at a first end of said integrated barrel-stator and a secondopen end at a second end of said integrated barrel-stator and a sidewalldefining an interior chamber adapted to receive a supply of fluid, saidstator being circular, said stator having a first side, said elongatebarrel second end terminating at a centerpoint of said stator at saidstator first side and providing an orifice, said stator first side beingcoplanar with said second end of said integrated barrel-stator, saidstator having a first stator port for communication with a mobile phasesupply, said stator in communication with a rotor at said orifice, saidstator at said second end of said integrated barrel-stator, saidintegrated barrel-stator having a first side on said elongate barrel,the first side of said integrated barrel-stator having a thickness, saidthickness sufficient to withstand an internal pressure of said elongatebarrel, said thickness sufficient to deform proportionally to a changein said internal pressure; a strain gauge, said strain gauge affixed tosaid integrated barrel-stator at said first side and adapted to detectdeflection consistent with a pressure change within said barrel; alongitudinal plunger slidably extending into said interior chamber atsaid first end of said integrated barrel-stator, said plunger being ofsubstantially uniform cross-section; and said rotor being circular, saidrotor having a surface adjacent said stator, said rotor having a firstchannel in said surface, said rotor rotatable with respect to saidstator about said centerpoint of said stator among a load position, aninterim position, and an injection position, said load position definedby said first stator port and said orifice communicating with said firstchannel, said interim position defined by said orifice exposed to asurface of the rotor; and said injection position defined by saidorifice and a second stator port communicating with said first channel.2. The integral nano-scale pump and injection valve of claim 1 furthercomprising: a first hard plastic seal about the plunger sized to fitwithin said barrel and to fit about said plunger; a flexible seal aboutthe plunger sized to fit within said barrel and to fit about saidplunger adjacent the first hard plastic seal; a second hard plastic sealabout the plunger sized to fit within said barrel and to fit about saidplunger adjacent the flexible seal; a driving disk having a boretherethrough sized to fit about said plunger without interference, saiddriving disk having a driving disk first end and a driving disk secondend, said driving disk sized to freely fit within said integratedbarrel-stator adjacent said barrel, said driving disk having a shouldernear said driving disk first end and a neck at said driving disk secondend, said neck sized to fit within said barrel and to contact said firsthard plastic seal, a threaded male sleeve having a bore therethroughsized to permit movement of said plunger without interference, saidthreaded male sleeve sized to a threaded female section within saidintegrated barrel-stator adjacent said barrel; and a spring contactingsaid shoulder of said driving disk and an end of said threaded malesleeve.
 3. The integral nano-scale pump and injection valve of claim 2,further comprising a pump actuator associated with a plunger-drivingpiston attached to said plunger.
 4. The integral nano-scale pump andinjection valve of claim 3, further comprising a valve actuatorassociated with a driveshaft attached to said rotor.
 5. The integralnano-scale pump and injection valve of claim 2 further comprising: saidstator having the second stator port in communication with a fifthstator port, a third stator port for communication with a samplereservoir, a fourth stator port for outflow, a sixth stator port forcommunication with a chromatography column, a seventh stator port forreturn from said chromatography column, and an eighth stator port foroutflow from said valve, said rotor having a second channel in saidsurface, and a third channel in said surface, said load position furtherdefined by said third stator port and said fourth stator portcommunicating with said second channel; and said injection positionfurther defined by said fifth stator port and said sixth stator portcommunicating with said second channel, and by said seventh stator portand said eighth stator port communicating with said third channel. 6.The integral nano-scale pump and injection valve of claim 5, furthercomprising a pump actuator associated with a plunger-driving pistonattached to said plunger.
 7. The integral nano-scale pump and injectionvalve of claim 6, further comprising a valve actuator associated with adriveshaft attached to said rotor.
 8. The integral nano-scale pump andinjection valve of claim 2 further comprising: said stator having thesecond stator port in communication with a fifth stator port via loop, athird stator port for communication with a sample reservoir, a fourthstator port for outflow, a sixth stator port for communication with achromatography column, a seventh stator port for return from saidchromatography column, and an eighth stator port for outflow from saidvalve, said rotor having a second channel in said surface, a thirdchannel in said surface, and a fourth channel in said surface; said loadposition further defined by said second stator port and said thirdstator port communicating with said second channel, and said fourthstator port and said fifth stator port communicating with said thirdchannel; and said injection position further defined by said fifthstator port and said sixth stator port communicating with said thirdchannel, and by said seventh stator port and said eighth stator portcommunicating with said fourth channel.
 9. The integral nano-scale pumpand injection valve of claim 8, further comprising a pump actuatorassociated with a plunger-driving piston attached to said plunger. 10.The integral nano-scale pump and injection valve of claim 9, furthercomprising a valve actuator associated with a driveshaft attached tosaid rotor.
 11. The integral nano-scale pump and injection valve ofclaim 2 further comprising: said stator having the second stator port incommunication with a fifth stator port via loop, a third stator port forcommunication with a sample reservoir, a fourth stator port for outflow,a sixth stator port for communication with a chromatography column, saidrotor having a second channel in said surface, and a third channel insaid surface, said rotor rotatable with respect to said stator aboutsaid centerpoint of said stator between a load position and an injectionposition, said load position further defined by said second stator portand said third stator port communicating with said second channel, andsaid fourth stator port and said fifth stator port communicating withsaid third channel; and said injection position further defined by saidfifth stator port and said sixth stator port communicating with saidthird channel.
 12. The integral nano-scale pump and injection valve ofclaim 11, further a pump actuator associated with a plunger-drivingpiston attached to said plunger.
 13. The integral nano-scale pump andinjection valve of claim 12, further comprising a valve actuatorassociated with said rotor.
 14. An integral nano-scale pump andinjection valve for high performance liquid chromatography comprising:an integrated barrel-stator, said integrated barrel-stator having anelongate barrel and a stator, said integrated barrel-statorintegrally-formed of a single piece of monolithic material, saidelongate barrel having a first open end at a first end of saidintegrated barrel-stator and a second open end at a second end of saidintegrated barrel-stator and a sidewall defining an interior chamberadapted to receive a supply of fluid, said stator being circular, saidstator having a first side, said elongate barrel second end terminatingat a centerpoint of said stator at said stator first side at an orifice,said stator first side being coplanar with said second end of saidintegrated barrel-stator, said stator at said second end of saidintegrated barrel-stator, said elongate barrel in communication with arotor at said orifice, said stator having a first stator port forcommunication with a mobile phase supply, said integrated barrel-statorhaving a first side on said elongate barrel, the first side of saidintegrated barrel-stator having a thickness, said thickness sufficientto withstand an internal pressure of said elongate barrel, saidthickness sufficient to deform proportionally to a change in saidinternal pressure; a strain gauge, said strain gauge affixed to saidintegrated barrel-stator at said first side and adapted to detectdeflection consistent with a pressure change within said barrel; alongitudinal plunger slidably extending into said interior chamber atsaid first end of said integrated barrel-stator, said plunger being ofsubstantially uniform cross-section; and said rotor being circular, saidrotor having a surface adjacent said stator, said rotor having a firstchannel in said surface, said rotor rotatable with respect to saidstator about said centerpoint of said stator among a load position, aninterim position, and an injection position, said load position definedby said first stator port and said orifice communicating with said firstchannel, said interim position defined by said orifice exposed to asurface of the rotor; and said injection position defined by saidorifice and a second stator port communicating with said first channel.15. The integral nano-scale pump and injection valve of claim 2 furthercomprising: said stator having the second stator port in communicationwith a fifth stator port, a third stator port for communication with asample reservoir, a fourth stator port for outflow, and a sixth statorport for communication with a chromatography column; said rotor having asecond channel in said surface; said load position further defined bysaid third stator port and said fourth stator port communicating withsaid second channel; and said injection position further defined by saidfifth stator port and said sixth stator port communicating with saidsecond channel.
 16. The integral nano-scale pump and injection valve ofclaim 15, further comprising a pump actuator associated with aplunger-driving piston attached to said plunger.
 17. The integralnano-scale pump and injection valve of claim 16, further comprising avalve actuator associated with a driveshaft attached to said rotor. 18.An integral nano-scale pump and injection valve for high performanceliquid chromatography comprising: an integrated barrel-stator, saidintegrated barrel-stator having an elongate barrel and a stator, saidintegrated barrel-stator integrally-formed of a single piece ofmonolithic material, said elongate barrel having a first open end at afirst end of said integrated barrel-stator and a second open end at asecond end of said integrated barrel-stator and a sidewall defining aninterior chamber adapted to receive a supply of fluid, said stator beingcircular, said stator having a first side, said elongate barrel secondend terminating at a centerpoint of said stator at said stator firstside and providing an orifice, said stator first side being coplanarwith said second end of said integrated barrel-stator, said statorhaving a first stator port for communication with a mobile phase supply,said stator in communication with a rotor at said orifice, said statorat said second end of said integrated barrel-stator, said integratedbarrel-stator having a first side on said elongate barrel, the firstside of said integrated barrel-stator having a thickness, said thicknesssufficient to withstand an internal pressure of said elongate barrel,said thickness sufficient to deform proportionally to a change in saidinternal pressure; a strain gauge, said strain gauge affixed to saidintegrated barrel-stator at said first side and adapted to detectdeflection consistent with a pressure change within said barrel; alongitudinal plunger slidably extending into said interior chamber atsaid first end of said integrated barrel-stator, said plunger being ofsubstantially uniform cross-section; and said rotor being circular, saidrotor having a surface adjacent said stator, said rotor having a firstchannel in said surface, said rotor rotatable with respect to saidstator about said centerpoint of said stator among a load position andan injection position, said load position defined by said first statorport and said orifice communicating with said first channel, and saidinjection position defined by said orifice and a second stator portcommunicating with said first channel.